The invention concerns a method and a device for position and/or type-selective control of the position and/or change of position of suspended particles in a multielectrode system with the features of the preambles of patent claims 1 or 9, and especially planar and three-dimensional microelectrode configurations in semiconductor chip size, or a method of moving, holding, measuring or sorting suspended artificial or living particles (e.g. cells) or organic particles of microscopic size in fluids. For individual handling and/or characterization of such particles, and especially for directing them in a field gradient or traveling electric field, dielectric polarization forces are used that are generated by alternating electric fields and amplified by resonance phenomena.
Two basic principles are currently known by which electrical handling and characterization of individual objects can be performed: 1. the generation of field gradients in high-frequency alternating fields (Pohl, H. P., Dielectrophoresis, Cambridge University Press [1978]) and 2. application of rotating fields with a tunable rotation frequency (Arnold, W.-M. and Zimmermann, U., Z. Naturforsch. 37c, 908 [1982]). Related fields, but not included here, like electrophoresis and other direct-voltage techniques can also be used in part for the named particles but are not comparable in their effectiveness.
The first principle mentioned above leads to asymmetric polarization of microparticles, producing, (depending on the nature of the polarization, motion in the direction of higher or lower field strength. This response is termed positive or negative dielectrophoresis (Pohl, H. P., Dielectrophoresis, Cambridge University Press [1978]) and has been used for more than 30 years to move and separate suspended dielectric bodies and cells. In recent years dielectrophoretic principles have come into wider use in the biological/medical field through the introduction of semiconductor microelectrode systems (Washizu, M. et al., IEEE Trans. IA, 25(4), 352 [1990]; Schnelle, T. et al., Biochim. Biophys. Acta 1157, 127 [1993]).
The second of the principles mentioned above, the application of rotating fields of variable frequency (this category also includes linear traveling fields (Hagedorn, R. et al., Electrophoresis 13, 49 [1992])), is used to characterize the passive electrical features of individual suspended particles, and especially of cells (Arnold, W.-M. and Zimmermann, U., Z. Naturforsch. 37c, 908 [1982]; Fuhr, G. et al., Plant Cell Physiol. 31, 975 [1990]). The principle can be summarized as follows. A particle is located in a circular electrode configuration with a rotating field with a speed of a few hertz to several hundred megahertz. Because of the viscosity of the solution, it reacts like the rotor of a dielectric asynchronous motor. In the case of cells with their extremely complex structure (cell wall, membrane, organelles, etc), the frequency spectra of the rotation (particle rotation as a function of the rotation frequency of the field) allow far-reaching conclusions about the physiology and the characteristics of individual components of the same (Arnold, W.-M. and Zimmermann, U., J. Electrostat. 21, 151 [1988]; Gimsa et al. in Schutt, W., Klinkmann, H., Lamprecht, I., Wilson, T., Physical Characterization of Biological Cells, Verlag Gesundheit GmbH, Berlin [1991]).
All alternating electric field methods make use of polarization forces resulting from the relaxation of induced charges. What is of disadvantage is the half width of the dielectric dispersions, which are approximately of the order of a frequency decade (Pohl, H. P., Dielectrophoresis, Cambridge University Press [1978]; Arnold, W.-M. and Zimmermann, U., J. Electrostat. 21, 151 [1988]). This means that differentiation or differentiated movement of different particles requires relatively large differences in the structure or the dielectric characteristics. A further problem, especially as the particle radius reduces, is that other forces (local flow, thermal motion, etc) gain in influence and even exceed the polarization forces at a particle radius of less than a micrometer. With colloidal particles, where polarizability is far less than that of biological cells, the disadvantage is that relatively high control voltages (three to ten times as high) have to be applied to achieve the same force effects.
This is the reason why the two principles mentioned above could only be used to date for relatively large particles, and why a possibility has long been sought of amplifying the field effects.